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Background <p>Rheumatoid arthritis (RA) is an auto-immune inflammatory disorder for which an effective cure is yet to be found. Trans-anethole (1-methoxy-4-(1E)-1-propen-1-yl-benzene), a key bioactive compound derived from the perennial plant <i>Foeniculum vulgare</i>, exerts multiple medicinal benefits. In this study, we investigated the therapeutic potential of exosomes derived from anethole-preconditioned human Wharton Jelly-derived mesenchymal stem cells (hWJMSCs) against RA-like inflammation in H<sub>2</sub>O<sub>2</sub>-treated synoviocyte HIG-82 cells.</p> Methods <p>The fennel samples were prepared and trans-anethole was purified using LC–ESI–MS/MS analysis. The MTT cell viability assays, hWJMSC derived exosomes, and expression analysis of cellular markers related to proliferation, stemness, apoptosis, and extracellular matrix (ECM)-degrading proteases were performed using Western blotting in HIG-82 cells.</p> Results <p>The results showed that anethole treatment significantly increased cell viability and expression of the MSC marker CD90 in a dose-dependent manner in HIG-82 cells. Cell stemness markers, including proliferation markers cyclin-D, proliferating cell nuclear antigen (PCNA), and minichromosome maintenance complex component 2 (MCM2) were enhanced, whereas p53 and p21 were decreased by anethole. Exosomes derived from anethole-preconditioned hWJMSCs significantly improved the cell viability of H<sub>2</sub>O<sub>2</sub>-treated HIG-82 cells. Anethole- preconditioned exosomes decreased ECM-degrading proteases MMP-13, ADAMTS-2, -8, and -17, and AQP-3 expression more significantly than exosomes without preconditioned hWJMSC. Bcl-2 was increased, whereas Bax, Cyto c, and c-caspase 3 were decreased by preconditioned exosomes more prominently than exosomes from without preconditioned hWJMSCs in H<sub>2</sub>O<sub>2</sub>-treated HIG-82 cells.</p> Conclusion <p>Together, the study showed that exosomes derived from anethole-preconditioned hWJMSC have a greater potential to inhibit RA-like inflammation and apoptosis in H<sub>2</sub>O<sub>2</sub>-treated HIG-82 cells.</p>

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Trans-anethole enhances mesenchymal stem cell derived exosomes function to inhibit H2O2-induced rheumatoid arthritis-like inflammation in HIG-82 synovial cells

  • 期刊论文

  • 发表日期：

    2025年4月28日

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  • Tai-Lung Huang,
  • Yu-Chun Chang,
  • Wei-Wen Kuo,
  • Shih-Wen Kao,
  • Chia-Hua Kuo,
  • Dennis Jine-Yuan Hsieh,
  • Kuan-Ho Lin,
  • Tsung-Jung Ho,
  • Chih-Yang Huang

摘要

Background

Rheumatoid arthritis (RA) is an auto-immune inflammatory disorder for which an effective cure is yet to be found. Trans-anethole (1-methoxy-4-(1E)-1-propen-1-yl-benzene), a key bioactive compound derived from the perennial plant Foeniculum vulgare, exerts multiple medicinal benefits. In this study, we investigated the therapeutic potential of exosomes derived from anethole-preconditioned human Wharton Jelly-derived mesenchymal stem cells (hWJMSCs) against RA-like inflammation in H2O2-treated synoviocyte HIG-82 cells.

Methods

The fennel samples were prepared and trans-anethole was purified using LC–ESI–MS/MS analysis. The MTT cell viability assays, hWJMSC derived exosomes, and expression analysis of cellular markers related to proliferation, stemness, apoptosis, and extracellular matrix (ECM)-degrading proteases were performed using Western blotting in HIG-82 cells.

Results

The results showed that anethole treatment significantly increased cell viability and expression of the MSC marker CD90 in a dose-dependent manner in HIG-82 cells. Cell stemness markers, including proliferation markers cyclin-D, proliferating cell nuclear antigen (PCNA), and minichromosome maintenance complex component 2 (MCM2) were enhanced, whereas p53 and p21 were decreased by anethole. Exosomes derived from anethole-preconditioned hWJMSCs significantly improved the cell viability of H2O2-treated HIG-82 cells. Anethole- preconditioned exosomes decreased ECM-degrading proteases MMP-13, ADAMTS-2, -8, and -17, and AQP-3 expression more significantly than exosomes without preconditioned hWJMSC. Bcl-2 was increased, whereas Bax, Cyto c, and c-caspase 3 were decreased by preconditioned exosomes more prominently than exosomes from without preconditioned hWJMSCs in H2O2-treated HIG-82 cells.

Conclusion

Together, the study showed that exosomes derived from anethole-preconditioned hWJMSC have a greater potential to inhibit RA-like inflammation and apoptosis in H2O2-treated HIG-82 cells.